New study finds higher cancer risk in PSC with advanced dysplasia
Researchers say liver transplant may help prevent bile duct cancer in PSC
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Liver transplant may help prevent bile duct cancer in people with primary sclerosing cholangitis (PSC) who have advanced bile duct dysplasia, a serious precancerous change where cells appear more abnormal and grow more quickly, according to a new study.
But the study also found that many people with mild bile duct dysplasia may receive liver transplants they don’t actually need, because later testing showed no clear signs of precancer or cancer.
“The low diagnostic accuracy and unpredictable detection of mild dysplasia support a cautious, individualized approach to LT [liver transplant] in precancerous stages of PSC, while more advanced dysplasia remains a valid indication for [liver transplant],” the researchers wrote.
The findings come from the study, “A retrospective evaluation of preemptive liver transplantation for bile duct dysplasia in primary sclerosing cholangitis: Balancing risks and benefits,” published in JHEP Reports.
PSC raises risk of bile duct cancer over time
PSC is a liver disease that causes long-term inflammation and scarring of the bile ducts, the tubes that carry bile from the liver to the small intestine. Over time, this damage raises the risk of cholangiocarcinoma, a cancer that forms in the bile ducts inside or outside the liver.
Some people with PSC develop abnormal cellular changes in the bile ducts called dysplasia. Dysplasia may be low-grade (milder) or high-grade (more advanced). High-grade dysplasia is considered a stronger warning sign that cancer may develop.
However, “malignant transformation in the bile duct is difficult to distinguish from benign disease progression in PSC as symptoms and imaging features poorly differentiate benign from malignant bile duct [narrowing],” the researchers wrote.
Liver transplant, the only curative treatment for PSC, may prevent dysplasia from progressing into bile duct cancer.
“Individuals with PSC and bile duct dysplasia are at some centers recognized as candidates for preemptive [preventive] LT to avoid future, potentially incurable CCA [cholangiocarcinoma],” the researchers wrote. “This practice was introduced in Norway and Sweden in the early 2000s, and was rationalized by the poor prognosis of advanced CCA and the inability to diagnose early CCA, combined with short LT waitlist time and low waitlist mortality.”
Researchers review transplant outcomes to guide decision-making
To help doctors decide when a liver transplant may be most appropriate in PSC, researchers in Sweden and Norway retrospectively reviewed the medical records of 512 adults with PSC who received their first liver transplant between 2000 and 2021 at Oslo University Hospital and Karolinska University Hospital.
Most participants were men (76%) and had large-duct PSC (88%). On average, they underwent liver transplant about 10.6 years after their PSC diagnosis. In total, 88 people (17.2%) were indicated for liver transplant because of low-grade (5.7%) or high-grade bile duct dysplasia (11.5%).
The team then compared biopsy results taken before transplant with what pathologists later found when examining the removed livers and bile ducts under a microscope.
Among the 29 people transplanted for low-grade bile duct dysplasia, 12 (41.4%) had no abnormal or cancerous cells in the removed liver. Even among the 59 people with suspected high-grade bile duct dysplasia, 14 (23.7%) also had no signs of dysplasia or cholangiocarcinoma in the removed liver.
Overall, “nearly one-third of patients transplanted for suspected bile duct dysplasia had no [tissue] evidence of [cancer] in the [removed bile ducts],” the researchers wrote.
However, a small number (10.3%) of patients who were believed to have low-grade dysplasia were later found to have more serious disease, either high-grade dysplasia (3.4%) or cholangiocarcinoma (6.9%). This suggests “that accelerated progression to [cancer] is relatively uncommon in [low-grade dysplasia],” the team wrote.
Advanced dysplasia more often linked to hidden cancer
In people transplanted because tests suggested high-grade dysplasia, nearly half (47.4%) were confirmed to have either high-grade dysplasia (32.2%) or cholangiocarcinoma (15.3%) in the removed liver. This supports high-grade dysplasia as “a less questionable primary indication for LT,” the researchers wrote.
Five years after liver transplant, most of the 512 patients (95%) who had no cancerous cells in the removed liver were still alive. Survival was also high among people whose livers showed bile-duct dysplasia — 89% for low-grade dysplasia and 85% for high-grade dysplasia. By comparison, five-year survival rates were much lower (33%) for people whose livers already showed cholangiocarcinoma.
These findings suggest that liver transplant may help prevent cancer from developing and support survival in people with PSC who have accurately diagnosed high-grade bile duct dysplasia. However, the results also show that many people transplanted for low-grade dysplasia did not actually have confirmed dysplasia or cancer in the removed liver, meaning some may undergo major surgery without clear evidence of precancerous disease.
Because of this, doctors recommend a more cautious and individualized approach to liver transplant in people with low-grade dysplasia. In contrast, transplant “appears more clearly justified in accurately diagnosed [high-grade dysplasia], given its strong association with early malignancy and the poor prognosis of advanced [cholangiocarcinoma],” the researchers concluded.
